Journal of Obstetrics and Gynaecology

ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: https://www.tandfonline.com/loi/ijog20

A systematic review of the efficacy of alternative

medicine in the treatment of nausea and vomiting
of pregnancy

Fahimeh Khorasani, Hossein Aryan, Abousaleh Sobhi, Reihaneh Aryan,

Arefeh Abavi-Sani, Masumeh Ghazanfarpour, Masumeh Saeid & Fatemeh
Rajab Dizavandi

To cite this article: Fahimeh Khorasani, Hossein Aryan, Abousaleh Sobhi, Reihaneh Aryan, Arefeh
Abavi-Sani, Masumeh Ghazanfarpour, Masumeh Saeid & Fatemeh Rajab Dizavandi (2019): A
systematic review of the efficacy of alternative medicine in the treatment of nausea and vomiting of
pregnancy, Journal of Obstetrics and Gynaecology, DOI: 10.1080/01443615.2019.1587392

To link to this article: https://doi.org/10.1080/01443615.2019.1587392

Published online: 19 Jun 2019.

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JOURNAL OF OBSTETRICS AND GYNAECOLOGY
https://doi.org/10.1080/01443615.2019.1587392

ORIGINAL ARTICLE

A systematic review of the efficacy of alternative medicine in the treatment of

nausea and vomiting of pregnancy
Fahimeh Khorasania, Hossein Aryanb, Abousaleh Sobhic, Reihaneh Aryanb, Arefeh Abavi-Sanid,
Masumeh Ghazanfarpoura, Masumeh Saeide and Fatemeh Rajab Dizavandif
a
Department of Nursing and Midwifery, Razi School of Nursing and Midwifery, Kerman University of Medical Sciences, Kerman, Iran;
b
Department of General Physicians, Mashhad University of Medical Sciences, Mashhad, Iran; cDepartment of Anesthesiology, Mashhad
University of Medical Sciences, Mashhad, Iran; dDepartment of Pediatrics, Mashhad University of Medical Sciences, Mashhad, Iran;
e
Department of Medical Education, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran; fDepartment of Community
Health and Psychiatric Nursing, School of Nursing and Midwifery, Mashhad University of Medical Sciences, Mashhad, Iran

ABSTRACT KEYWORDS
To assess the efficacy alternative medicine in the treatment of nausea and vomiting of pregnancy Herbal medicine; nausea;
(NVP), three major databases of PubMed, Cochrane Library and Scopus were systematically searched vomiting; pregnant women;
since inception until January 14 2019 to investigate the effects of herbal medicines on NVD. The qual- systematic review;
phytoestrogen
ity assessment of studies was performed according to Jadad scale. All studies showed that ginger had
a positive effect on nausea in pregnant women. Unlike others studies, one study reported that ginger
was not beneficial to the treatment of vomiting. Herbal medicines such as matricaria chamomilla, elet-
taria cardamomum, pomegranate and spearmint syrup, lemon provide safe and effective medical alter-
natives for treating pregnant women with mild to moderate NVD. The results suggested that ginger
were more effective than vitamin B, but at the dose of 35–500 mg ginger, vitamin B6 and ginger had
identical effect. However, over a longer treatment period (60 days), vitamin B6 was proved to be more
effective than ginger. The same effect was observed in the comparison of quince and vitamin B6 as
well as ginger and doxylamine plus pyridoxine. Mentha did not generated a positive effect on nausea
and vomiting. However, this finding should be considered in the light of the above limitations.

IMPACT STATEMENT

What is already known on the subject? Previous systematic reviews have shown the superiority
of ginger over the placebo. Lemon, chamomile and Mentha have been found to be more effective
than the placebo.

What do the results of this study add? This systematic review confirmed the results of previous
systematic reviews in a larger sample size. Ginger was more effective than vitamin B, but at the
dose of 35–500 mg ginger, vitamin B6 and ginger had identical effect. However, over a longer
treatment period (60 days), vitamin B6 was proved to be more effective than ginger.

What are the implications of these findings for clinical practice and further research?
Matricaria chamomilla, elettaria cardamomum, pomegranate and spearmint syrup, lemon and gin-
ger can be recommended to pregnant women for alleviation of NVP.

Introduction (Herrell 2014). According to the statistics reported in the United

Nausea and vomiting of pregnancy (NVP) is a common problem States, the total economic burden of NVP was estimated at
for the pregnant women (Golmakani et al. 2016). The causes of $1,778,473,782 in 2012 (Piwko et al. 2013). Severe cases of NVP
NVP are unclear due to the multiplicity of factors involved have been shown to be associated with maternal problems,
including rapid release of body hormones like oestrogen and adverse effects on the foetus and complications such as low
human chorionic gonadotropin (hCG) (Golmakani et al. 2016). birth weight, preterm birth, maternal malnourishment, and even
NVP commonly appears at the sixth to eighth weeks of preg- maternal renal failure, oesophageal rupture and coagulopathy
nancy and reaches its peak at about the ninth week of preg- (Viljoen et al. 2014). NVP can also exert an adverse effect on the
nancy (Jarvis and Nelson-Piercy 2011). It is the most prevalent quality of life of pregnant women in terms of social behaviour,
pregnancy symptom that affects about 50% to 90% of the family relationship and general health status. Accordingly, it is
pregnant women (Jiang et al. 2016). NVP is rarely seen after essential to address this serious concern (Saberi et al. 2013).
twentieth week of pregnancy (Abdolhosseini et al. 2017). The non-pharmacological therapy of NVP during preg-
Less educated, old and black women and those from lower nancy is underpinned by a change of nutritional habits, life-
social classes and multiple pregnancies are at higher risk of NVP style and medications, which have received scant attention in

CONTACT Masumeh Ghazanfarpour [email protected], [email protected] Department of Nursing and Midwifery, Razi School of Nursing
and Midwifery, Kerman University of Medical Sciences, Kerman, Iran
ß 2019 Informa UK Limited, trading as Taylor & Francis Group
2 F. KHORASANI ET AL.

the literature (Soltani et al. 2017). The drugs widely used to Quality assessment
treat the mild to moderate cases of NVP are pyridoxine, anti-
The quality of articles was assessed based on the Jadad scale
histamines, metoclopramide, pyridoxine/doxylamine, pro-
(Jadad et al. 1996), which consists of three main domains of
methazine and metoclopramide. In the event of more severe
randomisation (method of randomisation and appropriate-
symptoms, ondansetron and corticosteroids can be pre-
ness of randomisation), blinding (method of blinding and
scribed. However, there is little on the efficacy of these drugs.
suitability of blinding) and dropouts or withdrawals. The
Many mothers feel helpless in dealing with this condition,
Jadad scale is scored on a scale of 0 to 1. The items were
especially out of concern for side effects of these drugs on
assessed by two researchers independently and any disagree-
the unborn foetus (Viljoen et al. 2014).
ment was resolved by a third party. In addition, intention to
Comparison of ginger with vitamin B6, (Sripramote and
treat and baseline comparability were included in the
Lekhyananda 2003; Smith et al. 2004; Chittumma et al. 2007;
Jadad scale.
Pongrojpaw et al. 2007; Ensiyeh and Sakineh 2009; Quality assessment of 11 studies is shown in Table 1.
Firouzbakht et al. 2014; Rukh et al. 2016) ginger with dimen-
hydrinate (Pongrojpaw et al. 2007), Ginger vs. doxylamine
plus pyridoxine (Biswas et al. 2011), quince vs. Vitamin B6 Data extraction
(Jafari-Dehkordi et al. 2017) and pomegranate and spearmint A pre-designed checklist was used independently by two
syrup plus vitamin B6 with alone vitamin B6 (Abdolhosseini authors to extract relevant data such as authors, year of pub-
et al. 2017) are one of advantages compared to previous sys- lication, age of patients, place of study (country and city),
tematic. Aim of the systematic review is to assess the efficacy study design (parallel or crossover), type of therapy, dose of
alternative medicine in the treatment of nausea and vomiting drugs, duration of study, percentage of dropout, instrument
of pregnancy (NVP). of study, number of subjects in case and control groups, pos-
sible complications and main outcomes.

Material and method Results

Search strategy Characteristics of 24 studies included in our systematic

review are shown in Table 2. In Figure 1, the process of
The search was undertaken by two separate reviewers on selecting these 24 studies in the systematic review has
PubMed, Cochrane Library, and Scopus databases since been shown.
inception until January 14, 2019 to investigate the effects of
herbal medicines on NVD, using keywords such as (Pregnant
OR pregnancy) AND (emesis OR anti-emetic OR Nausea OR
Zingiber officinale (ginger)
vomit OR morning sickness), AND (Complementary treat- Willetts divided patients randomly into two groups (A) ginger
ments OR alternative treatments OR phytomedicine, herbal group and (B) placebo group. The nausea experience score in
treatments, zingiber officinale OR Ginger OR Citrus lemon OR the ginger group was lower than the placebo group. There
lemon OR Matricaria chamomilla OR Citrus medica L OR alter- was also a significant drop in retching of the ginger group
native medicine OR complementary medicine OR Citron OR compared to the placebo group. There was no significant dif-
Cydonia oblonga mill OR Quince OR Elletaria cardamomum ference regarding vomiting (Willetts et al. 2003). Basirat et al.
OR Cardamom OR, Mentha spicata L. OR Spearmint OR, randomised 65 patients into ginger biscuits and placebo bis-
Mentha piperta L OR Mint OR Myristica fragrans Houtt OR cuits groups. The main outcomes were nausea score and fre-
Nutmeg OR Pistacia lentiscus Linn OR Mastic, Punica grana- quency of vomiting episodes, which were measured between
tum L OR Pomegranate OR Malus domestica Borkh OR Apple D1 (day0–day1), D2 (day0–day1), D3 (day0–day1) and D4
OR Piper cubeba) . The researchers reviewed all abstracts and (day0–day1). Intergroup comparison indicated a significant
then the full-texts of relevant articles were found. Any dis- difference at all time points ([D1, p ¼ .021], [D2, p ¼ .048], [D3,
agreement was resolved by a third party. p ¼ .0003] and [D4, p ¼ .023]). Intergroup comparison regard-
ing vomiting episodes did not reveal any significant differ-
ence at all time points ([D1, p ¼ .074], [D2, 0.384], [D3, 0.367]
and [D4, 0.556]) (Basirat et al. 2009). Mohammadbeigi et al.
Inclusion and exclusion criteria compared three groups of metoclopramide (n ¼ 34), ginger
(n ¼ 34) and placebo (n ¼ 34). Repeated measures ANOVA
In our systematic review, we included randomised controlled revealed that ginger was more effective than placebo
trials, with parallel and crossover designs, that investigated (Mohammadbeigi et al. 2011). Vutyavanich et al. (2001) rand-
the effect of herbal medicines on NVD, whether intervention omised patients into two groups of ginger (n ¼ 32) and pla-
group was an alone herbal medicine or herbal traditional, or cebo (n ¼ 35). The mean changes of nausea score was
combined with pharmacological drug regardless of the type measured between D1 (day0–day1), D2 (day0–day2), D3
of control group. Criteria exclusion was if intervention group (day0–day3) and D4 (day0–day4), with the results suggesting
was combination of two or more herbal. a significant difference between two groups at D3 and D4.
Table 1. Characteristics of 24 studies included in the systematic review.
Number of
subjects in
Authors/ intervention
country/years Age/Y Study design /control Type of intervention Control group Duration Drop out % Assessment tool Results
Firouzbakht Ginger ¼ 24 parallel 40/40/40 500 mg of Ginger Vitamin B6 4 days 5% VAS Comparison of three groups
et al. Vitamin B6 ¼ 24, (80 mg)/Placeb0 regarding the severity of nau-
2014, Iran Placeb0 ¼ 25 sea and vomiting treatment
length were different from
each other; however, compared
to placebo group, the severity
of nausea was significantly
lower in either the ginger or
vitamin B6 groups.
Abdolhosseini Pomegranate parallel 37/37 15 cc of Pomegranate Vitamin B6(60 mg) 1 week 26% PUQE-24 the PUQE-24 score and the visual
et al. syrup þ Vitamin syrup þ Vitamin analogue scale scores were sig-
2017, Iran B6 ¼ 26 and B6(60 mg) nificantly lower in the pom-
Vitamin B6 ¼ 27 egranate syrup plus vitamin B6
group than vitamin
Biswas et al. Ginger ¼ 21, parallel 34/29 450 of ginger per day A combination of 1week 19% VAS no significant difference between
2011, India Doxyamine-pyri- doxylamine 10 mg ginger group and a combin-
doxine ¼22 plus pyridox- ation of doxylamine
ine 10 mg plus pyridoxine.
Rukh et al. Ginger ¼48, parallel 30/30 1000 mg ginger vitamin B6 (75 mg) 60 days 0% PUQE Percentage of improvement of
2016, Vitamin B6 ¼ 47 or lactose vomiting was significantly
Pakistan higher in vitamin B6(80%) than
and ginger (76.66%)
group (p ¼ 0.001)
Jackson Not mentioned parallel 70 pregnant 1 g ginger per day placebo 4 days 5% VAS Nausea scores was significantly
2001, women lower in the ginger group than
Thailand divided placebo on days 3 (p¼.031)
two groups and 4 (p¼.05), and for whole
period (p¼.014). Compared to
placebo, the proportion of sub-
jects with vomiting showed a
greater decrease in the ginger
(37.5% vs 65.7%, p¼.021)
Fischer- For first period ¼ Cross-over with 30 250 mg ginger lactose 8 days wash- 10% relief scores Relief scores was found to be sig-
Rasmussen 27 Second period wash- out 2 days nificantly greater in ginger
et al. ¼ 25 out 2 day group compared to placebo (p
1991, ¼ .035).
Demnark
Sripramote and Ginger ¼ 27 parallel 68/70 500 mg of ginger vitamin B6 (10 mg) Three days 8% VAS visual analogue scales graded the
Lekhyananda Vitamin B6 ¼ 26 times per day for three times per severity of their nausea using
2003, three days day for three days before treatment and recorded
Thailand the number
The mean score change was
less in ginger 1.4 ±2.21, com-
pared with vitamin 2.0
Pongrojpaw Ginger ¼27, parallel 85/85 one capsule con- 50 mg dimenhydri- 7 days 12% VAS VAS was similar between ginger
et al. Dimenhydrinate tained 0.5 mg of nate twice daily and dimenhydrinate group. No
2007, ¼ 26 ginger powder significant difference was not
Thailand observed regarding vomiting
JOURNAL OF OBSTETRICS AND GYNAECOLOGY

episodes during the day 3–7 of

after treatment
(continued)
3
 4

Table 1. Continued.
Number of
subjects in
Authors/ intervention
country/years Age/Y Study design /control Type of intervention Control group Duration Drop out % Assessment tool Results
Ensiyeh and Ginger ¼ 25, parallel 35/35 ginger 1 g/day for vitamin B6 40 mg/day 4 days 6% VAS The decrease in the visual ana-
Sakineh Vitamin B6 ¼ 24 4 days for 4 days logue scores was significantly
2009, Iran greater in ginger group than
vitamin B6 (p¼.024). However,
comparison of two group was
F. KHORASANI ET AL.

significant regarding number

of nausea
Chittumma Ginger ¼ 23 parallel 63/63 325 mg of ginger 12.5 mg of vitamin 4 days 3% Rhodes Index Treatment with ginger was more
et al. Vitamin B6 ¼ 24 three times per B6 three times per effectiveness than with vitamin
2007, day for 4 days day for 4 days B6 (p<.05)
Thailand
Smith et al. Ginger ¼ 29. parallel 146/145 350 g of ginger 25 mg of vitamin B6 3 weeks 20% Rhodes Index The efficacy of ginger was similar
2004, Vitamin B6 ¼ 26 daily for 3 weeks in both group regarding nau-
Australia sea (Mean
Difference{MD} ¼ 0.2), retching
(MD¼ 0.3) and vomiting (MD
¼ 0.5).
Willetts et al. Ginger ¼ 33, parallel Intervention 125 mg gin- placebo 4 days 17.5% Rhodes Index Retching and nausea experience
2003 placebo ¼ 31 n ¼ 60, ger extract score was lower in ginger
Australia Control group compared to placebo.
n ¼ 60 Any significant difference was
not observed regard-
ing vomiting
Jafari-Dehkordi Quince¼ 27 parallel Quince¼ 45 Quince (1 tablespoon vitamin B6 (20 mg) /three times 85% PUQE-24 Quince showed more effectiveness
et al. vitamin B6 ¼ 27 vitamin a day the vitamin B6 at weeks
2017 Iran B6 ¼ 45 1(p<.001) and week 2(p¼.001)
Mohammadbei- Ginger ¼ 26 parallel 34/34/34 Ginger 200 mg (gin- placebo 5 days 0% Rhodes Repeated measure ANOVA
gi et al. placebo ¼ 26 ger essence) questionnaire showed that Ginger was more
2011, Iran effectiveness than placebo
Vutyavanich Placebo ¼ 28.6 parallel Intervention 250-mg capsule four placebo 4 days 6% VAS Comparison of two groups was
et al. Control ¼ 28.3 n ¼ 32 times daily/4 day significant only at D3 (day0–-
2001, Control day3) and D4 (day0–day4).
Thailand n ¼ 35
Basirat et al. 19-35 parallel 35/30 Ginger Biscuits: 0.5 g Placebo Biscuit 4 days 5% VAS Ginger were more effective than
2009, Iran of ginger five bis- placebo in reducing nausea
cuits daily for score and as efficacy as pla-
four days cebo regarding in reducing
number of vomiting episodes
Keating and 24–37 parallel 14/12 Tablespoon of syrup Water, honey 2 weeks 16% Scale of 1 67% of subjects ginger group has
Chez 250 mg ginger in and lemon through 10 stopped vomiting by 6 day
2002, USA 4–8 ounces of hot Number of compared to 20% of subjects
and cold water 4 vomiting in the placebo group.
times a day, honey episodes
and water
Modares et al. Ginger¼ 23.6 ± 3.97 parallel 35/35/35 Ginger capsules twice placebo 7 days Patients Rhodes index total Rhodes index dropped sig-
2012, Iran Placebo¼ per day chamomile dropped out nificantly in Ginger group (3.14
24.8 ± 4.44, pla- capsule / 500 mg replaced by points) compared to 1.24 point
cebo ¼ 24.8 ± 4.44 of dried flower of a new in placebo group
German patients
chamomile.
(continued)
Table 1. Continued.
Number of
subjects in
Authors/ intervention
country/years Age/Y Study design /control Type of intervention Control group Duration Drop out % Assessment tool Results
Saberi, Ginger ¼ 23, parallel 40/40/40 Each capsule contain Placebo ¼ lactose 4 days Ginger/92.5% Rhodes Index Ginger group differed from two
2014, Iran Placebo¼ 40 250 mg Ginger Capsule Placebo/10% other groups regarding all total
Control ¼ 40 /three capsules Control Group ¼ no Control/17% score and Three its subclass
per day intervention vomiting, nausea and retching.
Yavari Kia, Lemon/26.2 parallel 50/50 Lemon oil 2 drop Normal saline 4 days 0% PUQE-24 Comparison of total score of nau-
2014, Iran Control/25.7 placed on cotton/ sea and vomiting between the
three times groups showed a significant
deep breaths difference for 1,2,3,4 day
Joulaeerad peppermint oil parallel 28/28 peppermint oil Normal saline 4 days 0% PUQE-24 Comparison of two groups using
et al. /or placebo /or placebo Mann-Whitney Test showed no
2018, Iran statistically significant differ-
ence regarding score of vomit-
ing and nausea between two
groups (p¼.227).
Ozgoli et al. Ginger;24.1 parallel 32/35 4 ginger capsu- placebo 4 days 5% VAS Nausea intensity and vomiting
2009, Iran Control ¼ 23.3 les daily time improved significantly in
ginger compared to placebo
group, which was significant
(p<.01). Vomiting time showed
a greater decrease in ginger
group (50%) compared to pla-
cebo group (9%), which was
significant (p<.05)
Pasha et al. Mint Oil ¼ Control¼ parallel 30/30 a bowl of water with a bowl of water with 4 days 9% Visual Analogue 67 patients were divided into two
2012, Iran 4 drops of pure 4 drops of normal Scale (VAS) groups to receive intervention
mint oil beds near salineoil beds near and placebo. Severity of nausea
and vomiting was similar
before and after treatment
between two groups.
Ozgholy et al. Intervention ¼ Carda- parallel 60/60 Capsules containing placebo 4 days 8% Research–made Frequency and duration of nausea
2015, Iran mom ¼ 27 500 mg questionnaire and frequency of vomatining
Control¼ 26 Cardamom powder showed a significant in
Elettaria cardamomum in com-
parison placebo (p<.0001).
Visual analogue scales (VAS); 24-hour Pregnancy Unique Quantification of Emesis (PUQE-24); mean difference (MD).
JOURNAL OF OBSTETRICS AND GYNAECOLOGY
5
6 F. KHORASANI ET AL.

Table 2. Assessment of quality of studies using Jade scale.

Randomisation Blinding
Sample
Mention Method: Method: Method: Method: Account of
Author randomisation appropriate inappropriate Concealment Mention blinding appropriate inappropriate all patients
Abdolhosseini   – ?   – 
Fischer-  – – ?  – – 
Rasmussen
Jafari-Dehkordi  – – ? – – – 
Biswas  – –   – – 
Firouzbakht  – –    – 
Jackson   –    – 
Sripramote   –    – 
Rukh  – – ? – – – ?
Pongrojpaw  – –    
Ensiyeh Jenabi   –    – 
Chittumma      
Smith  – –   – – 
Modares   – ?   – 
Keating   –   – 
Basira   –    – 
Sabari   –  – – – 
Yavari Kia   –    – 
Joulaeerad,   –    – 
Vutyavanich   –   – – 
Ozgoli  – – ?   
Ozgholy   – ?   – 
Pasha  – –  – – 
Willetts   – ?   – 
Mohammadbeigi  – –  – – 
“” indicates that the specific criteria/aspect was noted in the study while “–” denotes the absence of the criteria/aspect. “?” shows that it was not possible to
evaluate the specific criteria/aspect.

relevant studies in the first

subclass of Rhodes Index of Nausea, Vomiting and Retching
search n=808 including retching distress, vomiting distress, duration of
nausea, nausea distress, amount of vomiting each time, fre-
Studies excluded by initial
screening of titles and
quency of nausea and frequency of retching dropped sig-
abstracts n=784 nificantly in the ginger group. The mean Rhodes Index
declined significantly in the ginger group (3.14 points)
Studies evaluated in detail n=24 compared to 1.24 point drop in the placebo group. Saberi
randomly assigned 120 women with nausea and vomiting
Studies excluded n=0
to three equal groups of ginger, placebo and control.
Comparison of three groups using ANOVA suggested a sig-
nificant difference with regard to the total Rhodes Index
Studies included in the review
systematic n=24
scores and its subclass of vomiting, nausea and retching.
ANOVA followed by Tukey’s post hoc test showed that gin-
Figure 1. Search strategy of the study.
ger group differed from the other two groups with respect
to all of above parameters (Saberi et al. 2014). ANCOVA
Ozgoli et al. (2009) compared the effect of ginger cap- with possible confounding variables such as age of mar-
sule and placebo on pregnant women. In their study, there riage and wanted or unwanted pregnancy demonstrated a
was 86% improvement in the nausea intensity in ginger significant difference in all of the above-men-
group compared to 56% improvement in the placebo tioned parameters.
group, which was significant (p < .01). Vomiting episodes Fischer-Rasmussen et al. (1991) assessed the effect of Ginger
dropped significantly in the ginger group (50%) compared treatment on women with hyperemesis gravidarum in a dou-
to the placebo group (9%) (p < .05). In Keating et al.’s ble-blind randomised cross-over trial. The first group received
study, 26 women with vomiting were randomly assigned to Ginger and the second group took placebo. Then, women were
the ginger syrup (n ¼ 14) and placebo syrup (n ¼ 12). Ten switched to another drug for four days. The wash-out period
out of 13 (77%) subjects in the ginger group reported a 4- was 2 days. Relief scores in the Ginger group were found to be
point improvement, while 7% subjects in the placebo significantly higher than that of the placebo (p ¼ .035).
group experienced a 2-point improvement. In 67% of sub- Jackson (2001) assessed the effect of ginger root on the
jects in the ginger group, vomiting stopped after 6 days, as severity of nausea and vomiting in early pregnancy. Nausea
compared to 20% of subjects in the placebo group. The scores in the ginger group were significantly lower than the
authors did not provide any inter-group comparison placebo on day 3 (p ¼ .031), day 4 (p ¼ .005), and during the
(Keating and Chez 2002). Modares et al. (2012) compared whole period (p ¼ .014). Compared to the placebo, there was
the effect of ginger (n ¼ 35) and placebo (n ¼ 35) on a dramatic decline in the proportion of subjects with vomit-
women with mild-to-moderate vomiting and nausea. All ing in the ginger group (37.5% vs. 65.7%, p¼.021)
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 7

Ginger vs. vitamin B6 with repeated measures ANOVA indicating a significant differ-
ence <.049).
In the first study by Chittumma et al. (2007), treatment with
ginger and vitamin B6 significantly improved nausea and
vomiting scores from 8.7 þ 2.2 to 5.4 þ 2.0 and 8.3 þ 2.5 to Mentha (piperita)
5.7 þ 2.3 respectively, (p<.05). However, treatment with gin-
Joulaeerad et al. (2018) compared the effect of Peppermint
ger was more effective than vitamin B6 (p < .05).
Oil inhalation and placebo on women with vomiting and
In the second study, Ensiyeh and Sakineh (2009) com-
nausea. The mean difference indicated a declining trend of
pared two groups of vitamin B6 (40 mg/day) and ginger (1 g/
vomiting and nausea in both Peppermint Oil group (7.36,
day of ginger) daily for 3 weeks. The decreased visual ana-
6.46, 6.11, 5.79 and 5.18) and the placebo group (7.21, 6.75,
logue scores in the ginger group was significantly greater
6.82, 5.75 and 5.82). Repeated measures ANOVA showed a
than that of vitamin B6 (p ¼ .024). However, the two groups
significant difference between days for both Lemon (p < .001)
were significantly different in terms of the frequency
and placebo (p < .001). The comparison of two groups using
of nausea.
Mann–Whitney test did not show any significant difference
In the third study of Sripramote and Lekhyananda (2003),
with regard to the score of vomiting and nausea in two
138 women were randomly allocated to two groups receiving
groups (p ¼ .227). The patients satisfied with their treatment
either 500 mg of ginger or vitamin B6 (10 mg) three times a
(n ¼ 60) in the lemon group outnumbered patients in the
day for three days. The mean score change in ginger group
placebo group (n ¼ 57), though the difference was not signifi-
(1.4 ± 2.21) was less than vitamin group (2.0 ± 2.19). However,
cant. Pasha et al. (2012) compared the effect of mint oil
the two groups were not significantly different (p ¼ .136). The
mean score change in the ginger (0.7 ± 2.18) was higher than (piperita) on nausea and vomiting in 67 patients. They div-
vitamin B6 group (0.5 ± 1.44). Nonetheless, the two groups ided subjects into two intervention and placebo groups. The
were not significantly different in this regard (p ¼ .498). severity of nausea and vomiting was identical in both groups
In contrast to above studies, Smith et al. (2004) compared before and after treatment.
two groups of vitamin B6 (25 mg) and ginger (350 g ginger)
for 3 weeks. The effect of ginger on nausea (mean differ- Matricaria chamomilla
ence¼ 0.2, 90% confidence interval [CI] 0.3, 0.8), retching
(mean difference ¼ 0.3; 90%CI 0.0, 0.6) and vomiting (mean Modares et al. (2012) compared the effect of chamomile and
difference ¼ 0.5; 90% CI 0.0, 0.9) was similar in both groups. placebo on women with mild to moderate vomiting and nau-
In the study of Firouzbakht et al. (2014), the three groups of sea. Score of all subclass of Rhodes Index (vomiting, distress
study were not significantly different with regard to the retching) in the chamomile group were lower than that of
severity of nausea and vomiting treatment length; however, the placebo group (p < .05).
compared to the placebo group, the severity of nausea was
significantly lower in either the ginger or vitamin B6 groups.
Elettaria cardamomum
Rukh et al. (2016) reported that the percentage of vomiting
improvement was significantly higher in vitamin B6 (80%) Ozgholy et al. (2015) randomised 120 pregnant women into
compared to the ginger group (76.66%) (p ¼ .001) two groups that were treated with Elettaria cardamomum
and placebo. Frequency and duration of nausea and the fre-
quency of vomiting in the group receiving Elettaria cardamo-
Ginger v.s. Dimenhydrinate mum was significantly lower compared to the placebo
Pongrojpaw et al. (2007) compared the effect of ginger and group (p < .0001).
dimenhydrinate on nausea and vomiting during pregnancy.
A total of 170 pregnant women were randomised into ginger
Quince vs. vitamin B6
group (n ¼ 85) and dimenhydrinate group (n ¼ 85). On day
1–7 of the treatment, the visual analogue nausea scores Jafari-Dehkordi et al. (2017) compared the effect of Quince (1
(VANS) were similar between ginger and dimenhydrinate tablespoon/three times a day) and vitamin B6 (20 mg/three
groups. On the first and second days, the vomiting episodes times a day) using the ‘Pregnancy-Unique Quantification of
in ginger group were greater than the dimenhydrinate group. Emesis’ (PUQE-24) questionnaire. They reported that quince
However, the two groups were not significantly different had higher effectiveness compared to vitamin B6 at week 1
regarding vomiting episodes during days 3–7 of treatment. (p < .001) and week 2 (p ¼ .001).

Citrus Limon (Limon) Pomegranate and spearmint syrup plus vitamin B6 vs.
alone vitamin B6
Yavarikia et al. (2014) randomised 100 pregnant women with
nausea and vomiting into two groups of lemon inhalation In Abdolhosseini et al.’s study (2017), the PUQE-24 score and
and placebo. Comparison of the mean total score of nausea the visual analogue scale scores in the groups of
and vomiting in the two groups showed a significant differ- Pomegranate and spearmint syrup plus vitamin B6 were sig-
ence between day 1 (p ¼ .02), day 2 (p ¼ .001), day 3 nificantly lower than alone vitamin B6 on day 7. However,
(p ¼ .002) and day 4 (p ¼ .002) in the Lemon group (p < .001) there was not significant difference between two groups
8 F. KHORASANI ET AL.

regarding the duration of nausea, frequency of vomiting, and times more effective in relieving NVD (Thomson et al. 2014).
frequency of retching. AlHajri et al. (2017) conducted a systematic review of five
studies in 2017, reporting a significant improvement in the
ginger group compared to the placebo group (p < .05).
Ginger versus doxylamine plus pyridoxine
Cochran updates the systematic review with eight studies in
In the study of Biswas et al. (2011), the comparison of the 2014, which supported conclusion of previous systematic
nausea and vomiting scores between ginger group and a review, the beneficial effect of the ginger on nausea and
doxylamine plus pyridoxine group did not show any signifi- vomiting, but the limited evidence on effectiveness
cant difference. (Matthews et al. 2014). Based on a meta-analysis in 2014,
Viljoen et al. concluded that ginger could significantly dimin-
ish nausea and vomiting compared to the placebo (Viljoen
Discussion et al. 2014). The current systematic review is in line with pre-
The purpose of this systematic review was to assess the effi- vious systematic reviews.
cacy of herbal medicines on the nausea and vomiting of
pregnancy. All studies suggested that ginger had a positive Limitations and suggestions for future research
effect on nausea. Contrary to the literature, one study
reported that ginger was not beneficial to the treatment of Some of studies might be missed, as we only searched three
vomiting. Lemon and cardamomum were effective in treating databases. All studies included into the systematic review
nausea and the vomiting in pregnant women. However, assessed the effect of herbal medicines on pregnant women
Mentha was not effective in alleviating nausea and vomiting. with mild-to-moderate nausea and vomiting. Therefore, it is
The antiemetic effect of ginger have been attributed to difficult to generalise the findings to the pregnant women
two active ingredients of 6-gingerol and galanoctone who had severe nausea and vomiting.
(Yamahara et al. 1989b, 1990; Huang et al. 1991). 75 mg/kg Self-reporting tools such as Rhodes Index and 24-hour
extract of ginger or gingerol fed orally to mice increased Pregnancy-Unique Quantification of Emesis (PUQE-24) have
gastrointestinal transport. In the ginger group, this effect was been developed specifically to assess the effect of treatments
the same or relatively smaller compared to the placebo on the NVD. Some studies utilised reliable and validated
group (Yamahara et al. 1990). Yamahar et al. compared the tools, such as visual analogue score. Almost all studies used
effect of three treatments (150 mg/kg of acetone extract of special inventor but none of them assessed the reliability and
ginger, 6-ginforl and 25 mg/kg of metoclopramid) on cyclo- validity of the study instrument. Some variables such as dur-
phosphamid-induced vomiting in the suncus. Both actone ation of marriage and unwanted pregnancy can be consid-
extract of ginger and 6-gingerol were effective in preventing ered as confounding variables affecting outcomes of the
vomiting. The ginger also showed serotonergic effect research (Saberi et al. 2014), which were not assessed in
(Yamahara et al. 1989a) and anti-hydroxytryptamine activity some studies. Only one study did exhibit was the significant
(Huang et al. 1991). effect of lemon on NVD. Further studies with a larger sample
Two studies (Yavari Kia et al. 2014; Joulaeerad et al. 2018) size are required to confirm these findings. Some studies
assessed the effect of aromatherapy on the nausea and vom- were methodologically flawed with insufficient, concealment
iting in pregnant women. According to the results of these and blinding and only one study was conducted with the
two studies, lemon inhalation aromatherapy (Yavari Kia et al. treatment intention. Therefore, future studies should be
2014) and mentha aromatherapy (Joulaeerad et al. 2018) was designed and described in accordance with consort guide-
effective in relieving nausea and vomiting. The minimum lev- lines. Almost all studies conducted in the context of Iran
els of aroma were able to trigger physical and psychological focussed on herbal medicines, which make the generalizabil-
response in the body. The inhalation of aromatic ingredients ity of findings difficult. Some studies (Willetts et al. 2003;
can affect receptor cells that send massages to the olfactory Yavari Kia et al. 2014) revealed a decreasing trend in both
area of the brain, thereby stimulating and controlling mem- herbal treatment and control groups, which may be related
ory, emotions, hormones, sex and heart rate, and subse- to overtime or placebo effect. Therefore, it is recommended
quently creating physical and mental changes (Yavari Kia et that future studies consider all three groups (intervention,
al. 2014). placebo and control) to assess the effect of time
and placebo.

Comparison with previous systematic review

Conclusion
A systematic review was published in the Cochran library in
2010 based on five trials that indicated the beneficial effect Herbal medicines such as matricaria chamomilla, elettaria car-
of the ginger on nausea and vomiting, but the evidence on damomum, pomegranate and spearmint syrup, lemon and
effectiveness was limited and inconclusive (Matthews et al. ginger provide safe and effective medical alternatives for
2014). A systematic review of four trials by Diag et al. in 2013 treating pregnant women with mild-to-moderate NVD. The
revealed that ginger was more effective than the placebo results suggested that ginger were more effective than vita-
(Ding et al. 2013). A meta-analysis of six trials in 2014 involv- min B, but at the dose of 35–500 mg ginger, vitamin B6 and
ing 508 pregnant women suggested that ginger was five ginger had identical effect. However, over a longer treatment
 JOURNAL OF OBSTETRICS AND GYNAECOLOGY 9

period (60 days), vitamin B6 was proved to be more effective clinical trial. Journal of Obstetrics and Gynaecology: The Journal of
than ginger. The same effect was observed in the comparison the Institute of Obstetrics and Gynaecology 37:1048–1052.
Jarvis S, Nelson-Piercy C. 2011. Management of nausea and vomiting in
of quince and vitamin B6 as well as ginger and doxylamine
pregnancy. British Medical Journal 342:1407–1412.
plus pyridoxine. Mentha did not generated a positive effect Jiang Q, Li J, Wang G, Wang J. 2016. The relationship between constitu-
on nausea and vomiting. However, this finding should be tion of traditional Chinese medicine in the first trimester and preg-
considered in light of the above limitations. nancy symptoms: a longitudinal observational study. Evidence-Based
Complementary and Alternative Medicine 2016:3901485.
Joulaeerad N, Ozgoli G, Hajimehdipoor H, Ghasemi E, Salehimoghaddam
Disclosure statement F. 2018. Effect of aromatherapy with peppermint oil on the severity of
nausea and vomiting in pregnancy: a single-blind, randomized, pla-
Authors has provided no conflict of the interest. cebo-controlled trial. Journal of Reproduction and Infertility 19:32–38.
Keating A, Chez RA. 2002. Ginger syrup as an antiemetic in early preg-
nancy. Alternative Therapies in Health and Medicine 8:89–91.
Matthews A, Dowswell T, Haas DM, Doyle M, O’Math una DP. 2014.
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